Vaccines to protect against viral infections have been effectively used to reduce the incidence of human disease. One of the most successful technologies for viral vaccines is to immunize animals or humans with a weakened or attenuated strain of the virus (a “live, attenuated virus”). Due to limited replication after immunization, the attenuated strain does not cause disease. However, the limited viral replication is sufficient to express the full repertoire of viral antigens and generates potent and long-lasting immune responses to the virus. Thus, upon subsequent exposure to a pathogenic strain of the virus, the immunized individual is protected from disease. These live, attenuated viral vaccines are amongst the most successful vaccines used in public health.
Influenza is an orthomyxovirus with three genera, types A, B, and C. The types are distinguished by the nucleoprotein antigenicity. Influenza B is a human virus and does not appear to be present in an animal reservoir. Type A viruses exist in both human and animal populations, with significant avian and swine reservoirs.
Annual influenza A virus infections have a significant impact in terms of human lives, between 500,000 and 1,000,000 die worldwide each year, and economic impact resulting from direct and indirect loss of productivity during infection. Of even greater concern is the ability of influenza A viruses to undergo natural and engineered genetic change that could result in the appearance of a virus capable of rapid and lethal spread within the population.
One of the most dramatic events in influenza history was the so-called “Spanish Flu” pandemic of 1918-1919. In less than a year, between 20 and 40 million people died from influenza, with an estimated one fifth of the world's population infected. The US military was devastated by the virus near the end of World War I, with 80% of US army deaths between 1918 and 1919 due to influenza infection. Because it is a readily transmitted, primarily airborne pathogen, and because the potential exists for the virus to be genetically engineered into novel forms, influenza A represents a serious biodefense concern.
The past two decades have seen the emergence of highly virulent avian H5N1 influenza viruses. H5N1 avian influenza first emerged in the human population when the virus crossed the avian to human species barrier in 1997. These viruses are currently endemic to poultry populations in South East Asia, where they initially emerged. Over the past decade, they have significantly broadened their host and geographic range with a current human mortality rate of approximately 60%. Compounding this threat is the resistance displayed by H5N1 viruses to both classes of influenza antivirals.
Current public and scientific concern over the possible emergence of a pandemic strain of influenza, poxviruses or other pathogenic or non-pathogenic viruses requires effective preventative measures. Another challenge regarding generating vaccines has been to generate vaccines that protects against more than one strain of a virus